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Functional loss of ubiquitin-specific protease 14 may lead to a novel distal arthrogryposis phenotype.
Turgut, Gozde Tutku; Altunoglu, Umut; Sivrikoz, Tugba Sarac; Toksoy, Guven; Kalayci, Tugba; Avci, Sahin; Karaman, Birsen; Gulec, Cagri; Basaran, Seher; Sayin, Gözde Yesil; Kayserili, Hulya; Uyguner, Zehra Oya.
Afiliación
  • Turgut GT; Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
  • Altunoglu U; Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
  • Sivrikoz TS; Department of Medical Genetics, Koç University School of Medicine (KUSoM), Istanbul, Turkey.
  • Toksoy G; Perinatology Unit, Department of Obstetrics and Gynecology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
  • Kalayci T; Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
  • Avci S; Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
  • Karaman B; Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
  • Gulec C; Department of Medical Genetics, Koç University School of Medicine (KUSoM), Istanbul, Turkey.
  • Basaran S; Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
  • Sayin GY; Department of Pediatric Basic Sciences, Institute of Child Health, Istanbul University, Istanbul, Turkey.
  • Kayserili H; Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
  • Uyguner ZO; Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Clin Genet ; 101(4): 421-428, 2022 04.
Article en En | MEDLINE | ID: mdl-35066879
Multiple congenital contractures (MCC) comprise a number of rare, non-progressive conditions displaying marked phenotypic and etiologic heterogeneity. A genetic cause can be established in approximately half of the affected individuals, attributed to genetic defects in the formation and functioning of the central and peripheral nervous system, neuromuscular junctions, skeletal muscles, and connective tissue. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human MCC phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. We describe a new, autosomal recessive MCC phenotype in three fetuses from two different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11, SCV002028347) in USP14, and sequencing of family members showed segregation with the phenotype. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay. We propose that herein described fetuses represent the first human phenotype of USP14 loss, with callosal anomalies and/or cortical malformations, multiple contractures, and recognizable dysmorphic facial features.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artrogriposis / Contractura Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Clin Genet Año: 2022 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Dinamarca
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artrogriposis / Contractura Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Clin Genet Año: 2022 Tipo del documento: Article País de afiliación: Turquía Pais de publicación: Dinamarca